The short version of acylated peptide fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-08-20 and is reviewed periodically as new material appears.
Pharmacological activity arises from agonism at the glucagon-like peptide-1 receptor, a G protein-coupled receptor expressed in the pancreas, the gastrointestinal tract, and the brainstem. Receptor activation raises intracellular cyclic adenosine monophosphate and enhances insulin release in a glucose-dependent manner, an effect that diminishes when blood glucose concentration is low. Other effects include slowed gastric emptying and hypothalamic satiety signalling. These pathways are described well. Receptor desensitisation rates across tissues, relative to the endogenous hormone, are still under investigation, and reported findings differ between laboratories.
The company that developed the compound filed it as a long-acting analogue, and it gained first approval in 2017 for type 2 diabetes. Later authorisations from several regulators extended the indication to chronic weight management, and the World Health Organization added the glucagon-like peptide-1 receptor agonist drug class to its model list of essential medicines in 2023. Production uses solid-phase peptide synthesis followed by side-chain conjugation and chromatographic purification. Supply constraints and cost differences across regions are well documented. Literature on long-term outcomes continues to grow, with many trials reporting surrogate endpoints rather than hard clinical endpoints.
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
| Property | Value | Notes |
|---|---|---|
| Molecular class | 31-amino-acid peptide | Modified glucagon-like peptide-1 analogue |
| Molecular mass | approximately 4114 Da | Calculated for the free peptide backbone |
| Appearance | white to off-white powder | Typical of purified lyophilised peptide batches |
| Solubility class | freely soluble in water | Aqueous solubility improves at slightly alkaline pH |
| Typical storage | -20 degrees Celsius, dry, dark | Protect from repeated freeze-thaw cycles |
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
Krugman, Paul, "The American Way of Economic war: Is Washington Overusing Its Most Powerful Weapons?" (review of Henry Farrell and Abraham Newman, Underground Empire: How America Weaponized the World Economy, Henry Holt, 2023, 288 pp.), Foreign Affairs, vol. 103, no. 1 (January/February 2024), pp. 150–156. Mulder, Nicholas. The Economic Weapon: The Rise of Sanctions as a Tool of Modern War (2022) also see online review
== History == Founded as the "Association of Clinical Biochemists", the association has evolved as biochemistry has changed with advances in laboratory medicine. Recognizing an increasing number of medical members, the name was changed in 2005 to "Association for Clinical Biochemistry". In 2007 the "Association of Clinical Scientists in Immunology" merged with the ACB. The membership expanded in 2010 with the merger with the "Association of Clinical Microbiologists". The broader nature of the membership contributed to its renaming as ACB in 2013. The name was abbreviated to the Association for Laboratory Medicine in 2024.
=== Common features === All RiPPs are synthesized first at the ribosome as a precursor peptide. This peptide consists of a core peptide segment which is typically preceded (and occasionally followed) by a leader peptide segment and is typically ~20-110 residues long. The leader peptide is usually important for enabling enzymatic processing of the precursor peptide via aiding in recognition of the core peptide by biosynthetic enzymes and for cellular export. Some RiPPs also contain a recognition sequence C-terminal to the core peptide; these are involved in excision and cyclization. Additionally, eukaryotic RiPPs may contain a signal segment of the precursor peptide which helps direct the peptide to cellular compartments. During RiPP biosynthesis, the unmodified precursor peptide (containing an unmodified core peptide, UCP) is recognized and chemically modified sequentially by biosynthetic enzymes (PRPS). Examples of modifications include dehydration (i.e. lanthipeptides, thiopeptides), cyclodehydration (i.e. thiopeptides), prenylation (i.e. cyanobactins), and cyclization (i.e. lasso peptides), among others. The resulting modified precursor peptide (containing a modified core peptide, MCP) then undergoes proteolysis, wherein the non-core regions of the precursor peptide are removed. This results in the mature RiPP.
Successful delivery of therapeutics to the intended target largely depends on the choice of the drug carrier. The criteria for an ideal drug carrier include maximum effect upon delivery of the drug to the target organ, evasion of the immune system of the body in the process of reaching the organ, retention of the therapeutic molecules from preparatory stages to the final delivery of the drug, and proper release of the drug for exertion of the intended therapeutic effect. Nanofibers are under study as a possible drug carrier candidate. Natural polymers such as gelatin and alginate make for good fabrication biomaterials for carrier nanofibers because of their biocompatibility and biodegradability that result in no harm to the tissue of the host and no toxic accumulation in the human body, respectively. Due to their cylindrical morphology, nanofibers possess a high surface area-to-volume ratio. As a result, the fibers possess high drug-loading capacity and may release therapeutic molecules over a large surface area. Whereas surface area to volume ratio can only be controlled by adjusting the radius for spherical vesicles, nanofibers have more degrees of freedom in controlling the ratio by varying both the length and the cross-sectional radius. This adjustability is important for their application in drug delivery system in which the functional parameters need to be precisely controlled. Preliminary studies indicate that antibiotics and anticancer drugs may be encapsulated in electrospun nanofibers by adding the drug into the polymer solution prior to electrospinning.
=== Selective norepinephrine reuptake inhibitors === Noradrenergic neurons are located in two major regions in the brain, the locus coeruleus and lateral tegmental. With administration of SNRIs, neuronal activity in the locus coeruleus is induced because of increased concentration of norepinephrine in the synaptic cleft. This results in activation of α2 adrenergic receptors, as discussed previously. Assays have shown that SNRIs have insignificant penchant for mACh, α1 and α2 adrenergic, or H1 receptors.
Sources: en.wikipedia.org
=== Pharmacokinetics === Pharmacokinetic data collected from animal studies performed in mice and rats revealed an oral Tmax of 15 minutes, an area under the curve of 2.943 mg·hr·L−1, and an elimination half-life of 1.3 hours. Pharmacokinetic testing has been able to help explain the longer acting pharmacologic effects of osemozotan as well as its increased potency. Osemozotan was shown to have increased duration of pharmacologic effects compared to azapirones and requires a substantially lower dose to produce its pharmacologic effects. This result suggests that patients may not have to take the medication as often throughout the day. In these studies, there was a difference in dosage amount required for the intended indication. Osemozotan does not metabolize to 1-(2-pyrimidinyl)-piperazine (1-PP), a common metabolite found with the azapirone class of medications that has affinity for receptors other than the 5-HT1A receptor, thus decreasing its specificity and increasing the risk of unwanted effects. Since osemozotan does not produce this metabolite, it has greater specificity toward the 5-HT1A receptor when compared to other anxiolytic medications.
== History == Methenamine was first discovered as a chemical compound in 1859. It was introduced for medical use as a urinary antiseptic under the name Urotropin in 1895. The drug was described as rapidly sterilizing and thereby restoring putrid and pus-filled urine to a normal appearance and constitution. A combination of methenamine with salicylic acid was also developed and introduced the same year. Methenamine was only used as a urinary antiseptic in cases of acidic urine, whereas boric acid was used to treat UTIs with alkaline urine. The drug name methenamine, a contraction of the chemical or scientific name hexamethylenetetramine, was formally introduced and designated by the United States Pharmacopeia (USP) by 1925 and replaced the prior name of the drug that was being used of hexamethylenamine. The alternative drug name hexamine was introduced in the British Pharmacopoeia (BP) by 1914 to be used instead of the commercial name Urotropin. Interest in methenamine declined after the discovery of the antibiotic penicillin in 1928 and it has been described as a "forgotten drug". However, there was a surge of interest in methenamine from the 1950s to the 1980s. The drug was formally approved by the Food and Drug Administration (FDA) for medical use in the United States in 1967. The topical form of methenamine for treatment of hyperhidrosis was introduced around 1965. Subsequently, there was another decline in interest in methenamine from 1980 until 2010.
It was thought that with fewer malocclusions, breastfed children may have a reduced need for orthodontic intervention. The report suggested that children with a well-rounded, "U-shaped" dental arch, which is found more commonly in breastfed children, may have fewer problems with snoring and sleep apnea in later life. A 2016 review found that breastfeeding protected against malocclusions. Breastfeeding duration has been correlated with child maltreatment outcomes, including neglect and sexual abuse.
The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism. CT works by activating the G-proteins Gs and Gq often found on osteoclasts, on cells in the kidney, and on cells in a number of regions of the brain. It may also affect the ovaries in women and the testes in men. The function of the CT receptor protein is modified through its interaction with Receptor activity-modifying proteins (RAMPs), forming the multimeric amylin receptors AMY1 (CT + RAMP1), AMY2 (CT + RAMP2), and AMY3 (CT+ RAMP3). Preclinical studies have suggested that dual amylin and calcitonin receptor agonists may be more effective than amylin receptor agonists for obesity and type II diabetes.
== Pharmacology == Dimethyl fumarate is metabolized to monomethyl fumarate (MMF) prior to entering systemic distribution. Dimethyl fumarate has been described a prodrug. Dimethyl fumarate is a precursor of monomethyl fumarate. Other prodrugs that metabolize to monomethyl fumarate have been developed to treat relapse-remitting multiple sclerosis, including diroximel fumarate which was approved by the FDA in October 2019. The precise mechanism of action of dimethyl fumarate is not clear. Dimethyl fumarate and monomethyl fumarate can activate the transcription factor (Nuclear factor erythroid-derived 2)-related factor 2 (Nrf2) pathway and monomethyl fumarate has been identified as a nicotinic acid receptor agonist in vitro. In mice that lack Nrf2 expression, however, dimethyl fumarate is still able to modulate the immune system, which indicates that Nrf2 is not required for its immunomodulatory action. For psoriasis, the mechanism of action is believed to be due to the interaction of monomethyl fumarate and the intracellular reduced glutathione of cells directly involved in the pathogenesis of psoriasis. The interaction with glutathione leads to the inhibition of nuclear translocation and the transcriptional activity of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Dimethyl fumarate and monomethyl fumarate have been shown to reduce the expression of micro-RNA-21, which is essential for the production of pathogenic cells in multiple sclerosis and psoriasis.
Sources: en.wikipedia.org
Meanwhile, life cycle reversal, in which polyps are formed directly from medusae without the involvement of sexual reproduction process, was observed in both Hydrozoa (Turritopsis dohrnii and Laodicea undulata) and Scyphozoa (Aurelia sp.1). Anthozoa have no medusa stage at all and the polyps are responsible for sexual reproduction. Spawning is generally driven by environmental factors such as changes in the water temperature, and their release is triggered by lighting conditions such as sunrise, sunset or the phase of the moon. Many species of Cnidaria may spawn simultaneously in the same location, so that there are too many ova and sperm for predators to eat more than a tiny percentage — one famous example is the Great Barrier Reef, where at least 110 corals and a few non-cnidarian invertebrates produce enough gametes to turn the water cloudy. These mass spawnings may produce hybrids, some of which can settle and form polyps, but it is not known how long these can survive. In some species the ova release chemicals that attract sperm of the same species. The fertilized eggs develop into larvae by dividing until there are enough cells to form a hollow sphere (blastula) and then a depression forms at one end (gastrulation) and eventually becomes the digestive cavity. However, in cnidarians the depression forms at the end further from the yolk (at the animal pole), while in bilaterians it forms at the other end (vegetal pole). The larvae, called planulae, swim or crawl by means of cilia.
== Stage credits == Twelfth Night – 2002 Nero (Another Golden Rome) – 2006 (San Francisco) Spring Awakening – 2006 The Nightingale – 2003, 2005 (workshop) 2006 (based on The Nightingale) Whisper House – 2010 (Old Globe Theatre, San Diego) Carson McCullers Talks About Love (with Suzanne Vega) – 2011 (Off-Broadway) Alice by Heart – 2012 Because of Winn-Dixie – 2013 American Psycho – 2013 Noir – 2015 The Taming of the Shrew – 2016 (Washington, DC) The Secret Life of Bees – 2019 (Atlantic Theater Company, New York), 2023 (Almeida Theatre, London) Memoirs of Amorous Gentlemen – 2026
Hell Heaven pilots a lobster/fiddler crab–themed Kaijuki called Devil Capture (デビルキャプチャー, Debiru Kyapuchā) in an attempt to kidnap Princess Erika and distract the Dekarangers, but is deleted by Deka Blue while Devil Capture is destroyed by the Pat Striker in its Driving Sword formation. Hell Heaven is voiced by Keikō Sakai (酒井 敬幸, Sakai Keikō). Rikomoian Kevakia (リコモ星人ケバキーア, Rikomo Seijin Kebakīa): A digitally-based chameleon-themed being from Planet Rikomo who is capable of traveling through the internet and emerging from computers, but is powerless outside of one. He uses Hell Heaven to distract the Dekarangers while he kidnaps Princess Erika and ransoms her for her family's Wellness Stone. His physical body is deleted by Deka Red and Blue, but he successfully transfers his data into his personal Kaijuki, Devil Capture 2 (デビルキャプチャー2, Debiru Kyapuchā Tsū), and becomes its AI. Nevertheless, he is destroyed by Dekaranger Robo. Kevakia is voiced by Kōji Tobe (戸部 公爾, Tobe Kōji). Anrian Beildon (アンリ星人ベイルドン, Anri Seijin Beirudon): A rhinoceros-themed criminal from Planet Anri who possesses an armored body and is charged with mass-murder on five planets. While working for the scientist Mano Mark, Beildon turns humans into gasoline for a share of his employer's profits and commits bank robberies to help Mark fund his work until the latter is deleted by the Dekarangers via the D-Bazooka. Beildon is voiced by Kenta Miyake (三宅 健太, Miyake Kenta).
Various groups within Christianity have practiced specific dietary restrictions for various reasons. The Council of Jerusalem in around 50 AD, recommended Christians keep following some of the Jewish food laws concerning meat. The early sect known as the Ebionites are considered to have practiced vegetarianism. Surviving fragments from their Gospel indicate their belief that – as Christ is the Passover sacrifice and eating the Passover lamb is no longer required – a vegetarian diet may (or should) be observed. However, orthodox Christianity does not accept their teaching as authentic. Indeed, their specific injunction to strict vegetarianism was cited as one of the Ebionites' "errors". At a much later time, the Bible Christian Church founded by Reverend William Cowherd in 1809 followed a vegetarian diet. Cowherd was one of the philosophical forerunners of the Vegetarian Society. Cowherd encouraged members to abstain from eating of meat as a form of temperance. Seventh-day Adventists are encouraged to engage in healthy eating practices, and lacto-ovo-vegetarian diets are recommended by the General Conference of Seventh-day Adventists Nutrition Council (GCNC). They have also sponsored and participated in many scientific studies exploring the impact of dietary decisions upon health outcomes. The GCNC has in addition adapted the USDA's food pyramid for a vegetarian dietary approach. However, the only kinds of meat specifically frowned upon by the SDA health message are unclean meats, or those forbidden in scripture.
Sources: en.wikipedia.org
It is a glucagon-like peptide-1 receptor agonist, often grouped with the incretin mimetics. Its backbone is modified from the human hormone to resist enzymatic degradation and to bind albumin. These two features distinguish it from the native peptide.
No. It shares high sequence identity but carries non-natural modifications that alter its stability and clearance. The naturally occurring hormone is broken down within minutes, while the synthetic analogue circulates far longer.
Attachment to serum albumin reduces renal filtration of the peptide and shields it from enzymatic breakdown. The consequence is a much longer interval between administrations than unmodified peptides allow. The precise contribution of binding affinity to overall duration is still being quantified.
差别集中在三处：第 8 位残基被非天然氨基酸取代，第 34 位换成精氨酸，第 26 位增加一条脂肪酸侧链。前两处改动降低酶解速率，侧链则通过白蛋白结合延长循环时间。综合结果是半衰期从约两分钟延长到约一周。